ELAINE PIRES LEON
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus(2023) AIKAWA, Nadia Emi; BORBA, Eduardo Ferreira; BALBI, Verena Andrade; SALLUM, Adriana Maluf Elias; BUSCATTI, Izabel Mantovani; CAMPOS, Lucia Maria Arruda; KOZU, Katia Tomie; GARCIA, Cristiana Couto; CAPAO, Artur Silva Vidal; PROENCA, Adriana Coracini Tonacio de; LEON, Elaine Pires; DUARTE, Alberto Jose da Silva; LOPES, Marta Heloisa; SILVA, Clovis Artur; BONFA, EloisaIntroduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature.Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE.Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated.Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI >= 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05).Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. (www.clinicaltrials.gov, NCT03540823).
- Anti-DNase I Antibody A New Serological Reactivity in Primary Sjogren Syndrome(2020) GRIFFO, Priscilla; VIANA, Vilma V. S. T.; PASOTO, Sandra G.; LEON, Elaine P.; BONFA, EloisaBackground and Objective: Primary Sjogren syndrome (pSS) is a systemic autoimmune rheumatic disease that particularly affects exocrine glands. Dry eye is one of the most important features of this syndrome, and a recent study reported reduced deoxyribonuclease I (DNase I) activity in the tear of patients with dry eye. We therefore postulated that patients with pSS might have antibodies targeting DNAse I. Methods: We have evaluated in a cross-sectional study 85 patients with pSS (2002 American-European Consensus Group Criteria), 50 rheumatoid arthritis (RA) patients (1987 American College of Rheumatology Criteria) without sicca symptoms, and 88 healthy volunteers. IgG anti-DNase I was detected by enzyme-linked immunosorbent assay using as antigen bovine pancreas enzyme and confirmed by immunoblotting. Results: Age and sex were alike in the 3 groups (p > 0.05). Anti-DNase I was detected in 43.5% of the pSS patients. In contrast, this reactivity was absent in all RA patients (p = 0.0001). Additional comparison of pSS patients with (n = 37) or without (n = 48) anti-DNase I showed that the former group had higher IgG serum levels (2293.2 +/- 666.2 vs 1483.9 +/- 384.6 mg/dL, p = 0.0001) and greater rate of non-drug-induced leukopenia (43% vs 19%, p = 0.02). A multivariate logistic regression analysis identified that only IgG levels were independently associated with anti-DNase I. Conclusions: We describe a high frequency of anti-DNase I antibodies in pSS patients associated with higher serum IgG levels. The lack of this reactivity in RA patients without sicca symptoms suggests that this antibody may be helpful in the differential diagnosis of these diseases.
- Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases(2021) TONACIO, Adriana Coracini; PEDROSA, Tatiana do Nascimento; BORBA, Eduardo Ferreira; AIKAWA, Nadia Emi; PASOTO, Sandra Gofinet; FERREIRA FILHO, Julio Cesar Rente; BARROS, Marilia Mantovani Sampaio; LEON, Elaine Pires; LOMBARDI, Suzete Cleusa Ferreira Spina; MENDRONE JUNIOR, Alfredo; AZEVEDO, Adriana de Souza; SCHWARCZ, Waleska Dias; FULLER, Ricardo; YUKI, Emily Figueiredo Neves; LOPES, Michelle Remiao Ugolini; PEREIRA, Rosa Maria Rodrigues; BARROS, Percival Degrava Sampaio; ANDRADE, Danieli Castro Oliveira de; MEDEIROS-RIBEIRO, Ana Cristina de; MORAES, Julio Cesar Bertacini de; SHINJO, Samuel Katsuyuki; MIOSSI, Renata; DUARTE, Alberto Jose da Silva; LOPES, Marta Heloisa; KALLAS, Esper Georges; SILVA, Clovis Artur Almeida da; BONFA, EloisaBackground Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality. Objective This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression. Methods and Results A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p< 0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05). Conclusion Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(> 80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas.
- Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome(2020) VOLKOV, Ilan; SEGURO, Luciana; LEON, Elaine P.; KOVACS, Laszlo; ROGGENBUCK, Dirk; SCHIERACK, Peter; GILBURD, Boris; DORIA, Andrea; TEKTONIDOU, Maria G.; AGMON-LEVIN, NancyBackground Specific anti-phospholipids antibodies (aPLs) are used as classification criteria of the antiphospholipid syndrome (APS). These aPLs, although essential for diagnosis, do not predict disease phenotypes, which may require specific therapies. Non-criteria aPLs are rarely evaluated and their role is yet to be defined. In the current study, we aimed to examine the association between criteria and non-criteria aPLs and APS phenotypes. Methods Serum samples from 188 subjects, 130 APS patients and 58 controls were analyzed for the presence of 20 aPLs (IgG and IgM isotypes to cardiolipin (CL), beta2-glycoprotein1 (beta 2GP1), phosphatidic acid (P-acid), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylserine (PS), annexin-5 (AN) and prothrombin (PT) using a line immunoassay (GA Generic Assays, Germany). Sero-positivity to the different aPLs/aPLs profiles was correlated to APS phenotypes (i.e. arterial thrombosis, CNS manifestations, venous thrombosis, relapsing disease, obstetric morbidity). Results In this cohort, arterial thrombosis was associated with accumulative number of >= 7/20 aPLs evaluated (OR 4.1; CI 95% 1.9-96, p = 0.001) as well as the sole presence of aPT (IgG) (OR 2.3;CI 95% 1.1-5.1, p = 0.03). CNS manifestations were linked with a profile of 4 aPLs (IgG): aPT, aPG, aPI and aAN (OR 2.6;CI 95% 1.1-6.3, p = 0.03). Symptom-free period of >= 3 years was linked with lower number of aPLs and the presence of aPI (IgG) (OR 3.0;CI 95% 1.08-8.1, p < 0.05) or aAN (IgG) (OR 3.4;CI 95% 1.08-10.9, p < 0.05). APS related pregnancy morbidity correlated with a profile of 2 aPLs (IgG): aCL and aPS (OR 2.9; CI 95% 1.3-6.5, p < 0.05) or the sole presence of aAN (IgG) (OR 2.8; CI 95% 1.02-8, p = 0.05). Conclusion In this study, we observed an association between specific criteria/non-criteria aPLs or aPLs profiles and clinical phenotypes of APS. Our data suggest that examination of a wider variety of aPLs may allow better characterization of APS.
- Performance of alpha-defensin lateral flow test after synovial fluid centrifugation for diagnosis of periprosthetic knee infection(2021) ABDO, Rodrigo Calil Teles; GOBBI, Riccardo Gomes; LEITE, Chilan Bou Ghosson; PASOTO, Sandra Gofinet; LEON, Elaine Pires; LIMA, Ana Lucia Lei Munhoz; BONFA, Eloisa; PECORA, Jose Ricardo; DEMANGE, Marco KawamuraBACKGROUND The quantitative alpha-defensin enzyme-linked immunosorbent assay (ELISA) demands a prior synovial fluid centrifugation, whereas this processing is not routinely required prior to the alpha-defensin lateral flow test. AIM To evaluate whether a prior synovial fluid centrifugation could lead the lateral flow performance to achieve comparable results to ELISA during periprosthetic joint infection (PJI) diagnosis. METHODS Fifty-three cases were included in this study: 22 classified as PJI and 31 classified as aseptic cases, according to Musculoskeletal Infection Society 2013 criteria. Synovial fluid samples were submitted to centrifugation, and the supernatant was evaluated by ELISA and lateral flow tests. The sensitivity (SE), specificity (SP) and accuracy of each method were calculated as well as the agreement between those two methods. RESULTS In all of the 31 samples from aseptic patients, alpha-defensin ELISA and lateral flow tests showed negative results for infection. Regarding the 22 infected patients, the lateral flow test was positive in 19 cases (86.4%) and the ELISA was positive in 21 (95.5%). Sensibility, SP and accuracy were, respectively, 86.4% (95%CI: 65.1%-97.1%), 100% (95%CI: 88.8%-100%) and 93.2% (95%CI: 82.8%-98.3%) for the lateral flow test and 95.5% (95%CI: 77.2%-99.9%), 100% (95%CI: 88.8%-100%) and 98.1% (95%CI: 89.9%-100%) for ELISA. An agreement of 96.2% between those methods were observed. No statistical difference was found between them (P = 0.48). CONCLUSION Alpha-defensin lateral flow test showed high SE, SP and accuracy after a prior synovial fluid centrifugation, achieving comparable results to ELISA. Considering the lower complexity of the lateral flow and its equivalent performance obtained in this condition, a prior centrifugation might be added as a valuable step to enhance the PJI diagnosis.
conferenceObject Anti-beta 2GP1-Domain-1 Antibodies Are a Marker Of APS Severity(2013) AGMON-LEVIN, Nancy; SEGURO, Luciana; ROSARIO, Cristina; MAHLER, Michael; GATTO, Mariele; TOMER, Nir; LEON, Elaine P.; DORIA, Andrea; KOVACS, Laszlo; COSTEDOAT-CHALUMEAU, Nathalie; GILBURD, Boris; SHOENFELD, Yehuda- SYSTEMIC SCLEROSIS-RELATED AUTO-ANTIBODIES ARE MARKERS OF NEW CLINICAL ASSOCIATIONS IN A COHORT OF 328 BRAZILIAN PATIENTS(2014) SILVA, C. M.; BORTOLUZZO, A. B.; VIANA, V. S.; PASOTO, S. G.; LEON, E. P.; BONFA, E.; SAMPAIO-BARROS, P. D.
- Clark CA, Laskin CA. Ovarian reserve in antiphospholipid syndrome: the jury is still out. Lupus 2015; 24: 773(2015) YAMAKAMI, L. Y. S.; SERAFINI, P. C.; ARAUJO, D. B. de; BONFA, E.; LEON, E. P.; BARACAT, E. C.; SILVA, C. A.
conferenceObject Is Uric Acid Level a Predictor of Long-Term Renal Outcome in Lupus Nephritis?(2017) LOPES, Michelle; GAVINIER, Samara; LEON, Elaine; VIANA, Vilma; BORBA, Eduardo Ferreira; BONFA, Eloisa- EBV reactivation serological profile in primary Sjogren's syndrome: an underlying trigger of active articular involvement?(2013) PASOTO, Sandra Gofinet; NATALINO, Renato Romera; CHAKKOUR, Henrique Pires; VIANA, Vilma dos Santos Trindade; BUENO, Cleonice; LEON, Elaine Pires; VENDRAMINI, Margarete Borges Gualhardo; LEVY NETO, Mauricio; BONFA, EloisaAntibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjogren's syndrome (pSS) were not established. We evaluated 100 pSS patients (American-European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5 %, p = 0.501; 2.6 +/- A 1.1 vs. 2.5 +/- A 1.1 AU/mL, p = 0.737) and anti-EBNA-1 IgG (92 vs. 94.4 %, p = 0.576; 141.3 +/- A 69.8 vs. 135.6 +/- A 67.5 RU/mL, p = 0.464). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed in patients than controls (36 vs. 4.5 %, p < 0.0001; 38.6 +/- A 57.4 vs. 7.9 +/- A 26.3 RU/mL, p < 0.0001). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p a parts per thousand yen 0.551), current prednisone dose (4.8 +/- A 6.9 vs. 5.1 +/- A 10.4 mg/day, p = 0.319), and current uses of prednisone (52.8 vs. 37.5 %, p = 0.148) and immunosuppressants (44.4 vs. 31.3 %, p = 0.201). ESSDAI values were comparable (p = 0.102), but joint activity was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-alpha-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.